The third Enterprise, a schooner, was built by Henry Spencer at Baltimore, Md., in 1799, and placed under the command of Lieutenant John Shaw.

On 17 December 1799, Enterprise departed the Delaware Capes for the Caribbean to protect United States merchantmen from the depredations of French privateers during the Quasi-War with France. Within the following year, Enterprise captured 8 privateers and liberated 11 American vessels from captivity, achievements which assured her inclusion in the 14 ships retained in the Navy after the Quasi-War.

Enterprise next sailed to the Mediterranean, raising Gibraltar on 26 June 1801, where she was to join other U.S. warships in writing a bright and enduring page in American naval history. Enterprise's first action came on 1 August 1801 when, just west of Malta, she defeated the 14-gun Tripolitan corsair Tripoli, after a fierce but one-sided battle. Unscathed, Enterprise sent the battered pirate into port since the schooner's orders prohibited taking prizes. Her next victories came in 1803 after months of carrying despatches, convoying merchantmen, and patrolling the Mediterranean. On 17 January, she captured Paulina, a Tunisian ship under charter to the Bashaw of Tripoli, and on 22 May she ran a 30-ton craft ashore on the coast of Tripoli. For the next month, Enterprise and other ships of the squadron cruised inshore bombarding the coast and sending landing parties to destroy enemy small craft.

On 23 December 1803, after a quiet interval of cruising Enterprise joined with frigate Constitution to capture the Tripolitan ketch Mastico. Refitted and renamed Intrepid, the ketch was given to Enterprise's commanding officer, Lieutenant Stephen Decatur, Jr., for use in a daring expedition to burn frigate Philadelphia, captured by the Tripolitans and anchored in the harbor of Tripoli. Decatur and his volunteer crew carried out their mission perfectly, destroying the frigate and depriving Tripoli of a powerful warship. Enterprise continued to patrol the Barbary Coast until July 1804 when she joined the other ships of the squadron in general attacks on the city of Tripoli over a period of several weeks.

Enterprise passed the winter in Venice, where she was practically rebuilt by May 1805. She rejoined her squadron in July and resumed patrol and convoy duty until August of 1807. During that period she fought (15 August 1806) a brief engagement off Gibraltar with a group of Spanish gunboats who attacked her but were driven off. Enterprise returned to the United States in late 1807, and cruised coastal waters until June 1809. After a brief tour in the Mediterranean, she sailed to New York where she was laid up for nearly a year.

Repaired at the Washington Navy Yard, Enterprise was recommissioned there in April 1811, then sailed for operations out of Savannah, Ga., and Charleston, S.C. She returned to Washington on 2 October and was hauled out of the water for extensive repairs and modifications ; when she sailed on 20 May 1812, she had been rerigged as a brig. At sea when war was declared on Great Britain, she cruised along the east coast during the first year of hostilities. On 5 September 1813, Enterprise sighted and chased HBM Brig Boxer. The brigs opened fire on each other, and in a closely fought, fierce and gallant action which took the lives of both commanding officers, Enterprise captured Boxer and took her into nearby Portland, Maine. Here a common funeral was held for Lieutenant William Burrows, Enterprise, and Captain Samuel Blyth, Boxer, both well known and highly respected in their services.

After repairing at Portland, Enterprise sailed in company with brig Rattlesnake, for the Caribbean. The two ships took three prizes before being forced to separate by a heavily armed ship on 25 February 1814. Enterprise was compelled to jettison most of her guns in order to outsail her superior antagonist. The brig reached Wilmington, N.C., on 9 March 1814, then passed the remainder of the war as a guardship off Charleston, S.C.

Enterprise served one more short tour in the Mediterranean (July-November 1815), then cruised the northeastern seaboard until November 1817. From that time on she sailed the Caribbean and the Gulf of Mexico, suppressing pirates, smugglers, and slaves; in this duty she took 13 prizes. Her long career ended on 9 July 1823, when, without injury to her crew, she stranded and broke up on Little Curacao Island in the West Indies.